Mullerian Inhibiting Substance (MIS) is a TGF-beta family hormone important in reproductive tract embryogenesis. A temporal correlation has been described between the postmenopausal decrease in MIS and the occurrence of epithelial ovarian cancer. In addition, these tumors demonstrate growth inhibition in vitro after treatment with recombinant human MIS (rhMIS). For these reasons, we have chosen MIS as a potential adjuvant treatment for human ovarian cancer. In this study, a pilot group of patients with stage III/IV ovarian cancer will be screened for MIS binding by flow cytometry, a putative modality for rapid selection of potentially MIS-responsive tumors. Patients who fail to bind MIS will be screened for mutations in the MIS type II receptor gene. This strategy is consistent with a recent report of familial colon cancer patients who have a high incidence of TGF-beta receptor mutations. Binding of MIS or its absence by flow cytometry will be correlated with the presence of wild type or mutant MIS receptor gene and with the presence or absence of growth inhibition in bioassays for functionality. Ultimately, the understanding of these relationships will aid in the design of a clinical trial of MIS as an anti-cancer therapeutic.